Dr. Chikaraishi's research uses molecular, biological,
and transgenic methods to study the transcriptional
regulation and function of a neuronal-specific enzyme,
tyrosine hydroxylase. Tyrosine hydroxylase catalyzes
the rate-limiting step in the synthesis of catecholamine
neurotransmitters that include dopamine, norepinephrine
and epinephrine. The laboratory has identified important
cis-acting regulatory sites that regulate tyrosine
hydroxylase transcription in cultured cells and transgenic
mice. Current work investigates how tyrosine hydroxylase
is induced by depolarization in cultured cells and
seeks to develop a brain slice preparations in which
gene expression can be modified by synaptic activity.
The laboratory has also generated TH deficient mice
which lack all catecholamines. The knock-out mice
die of cardiovascular failure in mid-gestation before
TH neurons function in neurotransmission, suggesting
that catecholamines serve an unappreciated role during
early embryonic development. Physiological and pharmacological
experiments are in progress to investigate the nature
of this dependence upon catecholamines during development.
Null mice are also used to create new lines of mice
that lack catecholamines in specific neuronal groups.
Such mice could serve as genetic models for Parkinson‚s
Disease or dysautonomia in which the TH+ cells of
the substantia nigra or sympathetic ganglia are lost.
Trainees actively participate in all aspects of the
research,particularly in formulating hypotheses and
desgning and executing experiments to test those hypotheses.
